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Year 5 Path Immunology > 2: Transplantation > Flashcards

2: Transplantation Flashcards

1
Q

What are the different types of transplantation (refering to donor-recipient relation)

A
  • Autografts
    • within the same individual
  • Isografts
    • between genetically identical individuals of the same species
  • Allografts
    • between different individuals of the same species
  • Xenografts
    • between individuals of different species
  • Prosthetic graft
    • plastic, metal
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2
Q

What are the different types of donors that can donate in allograft transplantations?

A

Allograft= recipiant is different individuum from same species

Donors can be

  • Deceased
    • DBD (donor after brain stem death)–> neurological criterial for death
    • DCD (donor after circulatory death) –> circulatory criteria for death
  • Living donor
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3
Q

What are the criteria that need to be met for being an organ donor?

A

Once death has been confimed

  1. Excluding of Infections (e.g. HIV, HBV)
  2. malignany
  3. drug abuse, overdose or poison
  4. disease of the transplanted organ
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4
Q

What would happen if an organ with the blood group of A woud be transplanted to someone with blood group B (and anti-A antibodies

A

Antibodies would bind to endothelial A antigens and cause

  • complement activation
  • Blood clotting and thrombus formation
    • immediate loss of organ due to vascular damage (no perfustion possible)
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5
Q

How are AB0 incompatible transplants performed today?

A

Remove the antibodies in the recipient (plasma exchange)

  • Good outcomes (even if the antibody comes back)
  • Kidney, heart, liver
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6
Q

What are the three importatnt Class I and Class II HLA antigens for transplantation?

A
  • Class I (A,B,C)– expressed on all cells
  • Class II (DR, DQ, DP) (on Antigen-Presenting cells, but can be upregulated on other cells under stress )
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7
Q

What are the three mainantigens that are involved in performing HLA matching)

A

Main three (in order of importance) (but others are also important) are

  1. HLA-DR
  2. HLA-B
  3. HLA-A
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8
Q

Explain the concept of (mis)matching of antigens in transplantations

A

Three molecules are taken into consideration:

  • HLA-A, HLA-B, HLA-DR

Every HLA: 2 Alleles (one from each parent)

so: A maximum of 6 Mismatches can be there (2 for each HLA gene)

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9
Q

What is the main problem in transplantations?

What is the overall mechanism behind it?

A

Rejection

  • Exposure to foreign HLA molecules results in an immune reaction to the foreign epitopes
  • The immune reaction can cause immune graft damage and failure = rejection
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10
Q

How is organ rejection after transplantation diagnosed?

A

Mainly: Via histological examination of a graft biopsy

    • Clinical signs (e.g. monitor kidney function, liver enzymes etc.)
  • Hear only possible with biopsy
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11
Q

What are the two ways you can classify rejections?

A
  1. Time-linked classification
    • Hyper-acute (directly when organ is implanted)
    • Actue (weeks to months)
    • Chronic (years-happens in almost all recipients)
  2. Type of immune reaction
    1. T-cell mediated
    2. Antibody mediated
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12
Q

What happens during T-cell mediated rejection?

What are the three phases?

A
  1. Phase 1: Antigen-Presenting cells present the foreign HLA molecules (on their own HLA molecules) to T-cells in lymphocytes
  2. Phase 2: Get activated and cause migration into tissues and

3: Phase 3: Recrtuitement of pro-inflammatory cells that cause tissue damage (with release of cytotoxic things)

Interstitial inflammation

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13
Q

Which inflammatory cells are invove in T-cell mediated rejection?

What is their respective role?

A
  • CD4+ -T-cells
    • infiltrate the graft
  • CD8+
    • cytotoxic: kill cells in graft
  • Macrophages
    • phagocytosis and proteolysis of cells
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14
Q

When can antibodies that are involved in organ rejection form?

How do you call them?

A

They can be there pre-transplantation (in “sensitised” patients)

Or after transplantation (de novo)

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15
Q

Explain the process of antibody-mediated organ rejection

A

Antibodies against HLA and AB antigens

Phase 1: Recogniton of foreign antigens
Phase 2: Prliferation of B cells with Ab production

Phase 3:

  • antibodies bind to antigens presnent on endothelial donor cells
  • leading to complement and macrophage activation and
    Intra-vascular pathology
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16
Q

What are the different time-frames that you can Sub-devide Transplant rejection in?

A
  1. Hyperacute (Min-h)
  2. Acute (under 6m)
  • Cellular (CD4 Type IV hypersensitivity)
  • Antibody-mediated (B-cell mediated)
  1. Chornic (>6m)

Graft-Versus host disease

17
Q

What is usually the pathophysiology of hyperacute transplant rejection?

How can the risk be minimised?

A

Proformed Antibody in recipient attack the graft and activate complements –> Theombosis and necrosis of tissue

Pervention by Crossmatch (ABO groups) and HLA-Matching

18
Q

What is the Mechanism and pathology seen in chornic transplant rejection?

A

Differnt immune and non-immune mechanisms after more of 6 months of transplant

Risk factors

  • Multiple acute rejections
  • Hypertension

Shows with

  • fibrosis
  • glomerulopathy, vasculopathy, ischaemia
  • bronchilitis obliterans (lung)
19
Q

What are the targets of the immunosupressant drugs given in acture and preventative treatment of organ rejection

A
  1. Targeting T cell activation and proliferation
    • mainly signaling pathways that lead to activation or interaction between antigen presenting cell and T-cell
  2. Targeting B cell activation and proliferation, and therefore antibody production
    • anti-CD20 antibodies –> destroy B cells
    • Plasma exchange (get rid of antibodies)
20
Q

What are the targets for immunosupressant drugs pre-transplantation?

A

•Induction agent (T-cell depletion or cytokine blockade)

21
Q

What are the treatments in the base-line immunosupressing of tranplant patients? (after recieving an organ)

A
  • Signal transduction blockade, usually a CNI (calcineurin) inhibitor: Tacrolimus or Cyclosporin; sometimes mTOR inhibitor (Rapamycin) –> inhibits activation of T cells
  • Antiproliferative agent: MMF or Azathioprine (T-cell antiproliferative)
  • Corticosteroids
22
Q

What are the main risks that are associated with immunosupression in patients that have recieved an organ transplant?

A
  1. Drug toxicity
  2. Development of malignancies
  3. Increased risk of infections
23
Q

What kind of infections are people on immunosupressive therapy after recieving an orgn transplant more suseptible to?

A
  • Increased risk for conventional infections
    • Bacterial, viral, fungal
  • Opportunistic infections – normally relatively harmless infectious agents give severe infections because of immune compromise
    • Cytomegalovirus
    • BK virus
    • Pneumocytis carinii (jirovecii)
24
Q

What are the common types of post-transplation malignancies?

A
  • Skin cancer
  • Post transplant lymphoproliferative disorder – Epstein Barr virus driven
  • others
25
Q

What are the most important antigenic determinants of rejection in transplant practice?

A
  • MHC matching/ HLA matching
  • (ABO blood group no longer as much as problem)
26
Q

How does the T-cell activation work in T-cell mediated transplant rejection?

Effect

A

T cell activation leads to

  1. Proliferation of cells
  2. Production of Cytokines
  3. Activation of B-cells
27
Q

What histopathological findings can be seen in T-cell mediated host rejection?

A
  1. Lymphocytic and Monocytic infiltration
  2. Intimal arteritis (inflammatory cells in intima of arteries
    3.
28
Q

What are the histopathological findings of antibody-mediated rejection?

A

Mainly: Intra-vascular (capillary) pathology

Swollen endothelial cells -→ glomerulitis

Capillary infiltration of B-cells

29
Q

What is the clinical difference between antibody and t-cell mediated rejection?

A

Clinically same presentation

BUT

T-cell mediated rejection usually can be controlled

Antibody-mediated rejection is a lot harder to control and often leads to slow decline

30
Q

How is donor-recipient matching done?

A
  1. Serum
  2. Flow cytometry
  3. Solid phase assays
31
Q

What is the process of Flow-citometry donor-recipient crossmatch?

A

Does recipient serum bind to donor lymphocytes?

32
Q

What is the process of Solid phase assay donor-recipient cross-match?

A

Does recipient serum bind to dono

33
Q

How is acute antibody-mediated rejection treated?

A
  1. Plasma exchange: remove of antibodies)
  2. B-cell depletion: rituximab (anti-CD-20)
  3. Inhibition of antibody production
  4. IVIG: Inhibition of Antibodies
  5. anti-C5 (complement inhibition)
34
Q

How is acute T-cell mediated rejection treated?

A
  • Steroids (3x 60mg/kg IV, then oral)
  • ATG/OKT3
35
Q

What treatment regiment is usually prescribed as induction and baseline rejection prevention?

A

Induction Agent

  • T-cells depleting agents: OKT3/ATG, anti CD-52
  • B-cell: anti-CD25 (anti-IL2R)

Baseline immunosuppression:

CNI inhibitor + MMF or Aza (immunosuppression), with or without low-dose steroids

36
Q

How are drug-related complications in transplant medicine managed?

A

Is possible

  1. Decrease drugs
    1. treat complication (e.g. chemotherapy)
37
Q

What is the treatmen of acute B-cell mediated transplant rejection?

A

IVIG, plasma exchange, anti-C5, anti-CD20

Year 5 Path Immunology (6 decks)

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